Epigenetics, the study of the chemical modification of specific genes or gene-associated proteins of an organism. Epigenetic modifications can define how the information in genes is expressed and used by cells. The term epigenetics came into general use in the early 1940s, when British embryologist Conrad Waddington used it to describe the interactions between genes and gene products, which direct development and give rise to an organism’s phenotype (observable characteristics). Since then, information revealed by epigenetics studies has revolutionized the fields of genetics and developmental biology. Specifically, researchers have uncovered a range of possible chemical modifications to deoxyribonucleic acid (DNA) and to proteins called histones that associate tightly with DNA in the nucleus. These modifications can determine when or even if a given gene is expressed in a cell or organism.

DNA wraps around proteins called histones to form units known as nucleosomes. These units condense …

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Types of epigenetic modifications

The principal type of epigenetic modification that is understood is methylation (addition of a methyl group). Methylation can be transient and can change rapidly during the life span of a cell or organism, or it can be essentially permanent once set early in the development of the embryo. Other largely permanent chemical modifications also play a role; these include histone acetylation (addition of an acetyl group), ubiquitination (the addition of a ubiquitin protein), and phosphorylation (the addition of a phosphoryl group). The specific location of a given chemical modification can also be important. For example, certain histone modifications distinguish actively expressed regions of the genome from regions that are not highly expressed. These modifications may correlate with chromosome banding patterns generated by staining procedures common in karyotype analyses. Similarly, specific histone modifications may distinguish actively expressed genes from genes that are poised for expression or genes that are repressed in different kinds of cells.

Epigenetic inheritance

It is clear that at least some epigenetic modifications are heritable, passed from parents to offspring in a phenomenon that is generally referred to as epigenetic inheritance, or passed down through multiple generations via transgenerational epigenetic inheritance. The mechanism by which epigenetic information is inherited is unclear; however, it is known that this information, because it is not captured in the DNA sequence, is not passed on by the same mechanism as that used for typical genetic information. Typical genetic information is encoded in the sequences of nucleotides that make up the DNA; this information is therefore passed from generation to generation as faithfully as the DNA replication process is accurate. Many epigenetic modifications, in fact, are spontaneously “erased” or “reset” when cells reproduce (whether by meiosis or mitosis), thereby precluding their inheritance.

Impact of epigenetics on biomedicine

Epigenetic changes not only influence the expression of genes in plants and animals but also enable the differentiation of pluripotent stem cells (cells having the potential to become any of many different kinds of cells). In other words, epigenetic changes allow cells that all share the same DNA and are ultimately derived from one fertilized egg to become specialized—for example, as liver cells, brain cells, or skin cells.

As the mechanisms of epigenetics have become better understood, researchers have recognized that the epigenome—chemical modification at the level of the genome—also influences a wide range of biomedical conditions. This new perception has opened the door to a deeper understanding of normal and abnormal biological processes and has offered the possibility of novel interventions that might prevent or ameliorate certain diseases.

Epigenetic contributions to disease fall into two classes. One class involves genes that are themselves regulated epigenetically, such as the imprinted (parent-specific) genes associated with Angelman syndrome or Prader-Willi syndrome. Clinical outcomes in cases of these syndromes depend on the degree to which an inherited normal or mutated gene is or is not expressed. The other class involves genes whose products participate in the epigenetic machinery and thereby regulate the expression of other genes. For example, the gene MECP2 (methyl CpG binding protein 2) encodes a protein that binds to specific methylated regions of DNA and contributes to the silencing of those sequences. Mutations that impair the MECP2 gene can lead to Rett syndrome.

Many tumours and cancers are believed to involve epigenetic changes attributable to environmental factors. These changes include a general decrease in methylation, which is thought to contribute to the increased expression of growth-promoting genes, punctuated by gene-specific increases in methylation that are thought to silence tumour-suppressor genes. Epigenetic signaling attributed to environmental factors has also been associated with some characteristics of aging by researchers that studied the apparently unequal aging rates in genetically identical twins.

One of the most promising areas of epigenetic investigation involves stem cells. Researchers have understood for some time that epigenetic mechanisms play a key role in defining the “potentiality” of stem cells. As those mechanisms become clearer, it may become possible to intervene and effectively alter the developmental state and even the tissue type of given cells. The implications of this work for future clinical regenerative intervention for conditions ranging from trauma to neurodegenerative disease are profound.

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The term epigenetic is used to describe the dynamic interplay between genes and the environment during the course of development. The study of epigenetics highlights the complex nature of the relationship between the organism’s genetic code, or genome, and the organism’s directly observable physical and psychological manifestations and behaviours. In contemporary use, the term refers to...